Exploring molecular mechanisms of mouse hibernation for novel therapeutic angles in Alzheimer’s disease


Alzheimer’s disease is the most prevalent neurodegenerative disease worldwide. In spite of decades of research, there still is no effective treatment. This urges the need for novel research angles based on more out-of-the-box thinking. Interestingly, hibernation, a process in which animals undergo cycles of lowered metabolism and hypothermia, goes hand in hand with some fascinating brain adaptations that are of interest in this respect. 

This thesis of Christine de Veij Mestdagh focusses on identifying hibernation-derived mechanisms that may be of relevance for Alzheimer’s disease treatment. First, the effects of hibernation in mice on the brain are studied. Hibernation in mice was able to reverse toxic accumulation of tau protein in the brain, a key hallmark of Alzheimer’s disease. This points to the use of beneficial mechanisms relevant for Alzheimer’s disease treatment. 

Furthermore, it led to alterations in the way in which nerve cells communicate and produce energy. Interestingly, one cycle of hibernation was enough to restore memory in an Alzheimer’s disease mouse model. We then aimed to achieve the beneficial effects of hibernation on energy production in mice using a SUL compound that was designed to mimic hibernation. The compound restored communication between nerve cells and memory, and had a beneficial effect on energy production, similar to hibernation. In addition, it reduced Aβ protein plaques, the main pathological feature of Alzheimer’s disease, and normalized protein disruptions in the brain. 

The work in this thesis represents the first steps towards identification and use of hibernation-derived mechanisms for the future treatment of Alzheimer’s disease.